A literature search (Medline ) conducted at Indiana University and presented with the generous co-operation and permission of SilverPlatter.
Leigh's disease is a rare inherited neurometabolic disorder characterized by degeneration of the central nervous system. Symptoms of Leigh's disease, a rapidly progressive disorder, usually begin between the ages of 3 months and 2 years. In most children, the first noticeable signs may be poor sucking ability, loss of head control, and loss of previously acquired motor skills. These symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and/or seizures. As the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis. Lactic acidosis, the accumulation of lactic acid in the brain, may lead to impairment of respiratory and kidney function. Heart problems may also occur. In rare cases, Leigh's disease may begin during late adolescence or early adulthood. In these cases, the progression of the disease is slower than the classical form.
TITLE: Subacute necrotising encephalopathy in an Alaskan husky.
AUTHOR(S): Wakshlag-JJ; de-Lahunta-A; Robinson-T; Cooper-BJ; Brenner-O; O'Toole-TD; Olson-J; Beckman-KB; Glass-E; Reynolds-AJ
ADDRESS OF AUTHOR: Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
SOURCE (BIBLIOGRAPHIC CITATION): J-Small-Anim-Pract. 1999 Dec; 40(12): 585-9
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: A 29-month-old female Alaskan husky was presented recumbent, tetraparetic and in a state of dementia, with blindness and cranial nerve deficits. The dog's progress was followed for over two months, as the signs resolved to an non-progressive mild hypermetria with slight proprioceptive ataxia, a diminished menace response and inability to prehend food. Magnetic resonance imaging (MRI) revealed bilateral cavitation extending from the thalamus to the medulla, with less pronounced degenerative lesions in the caudate nucleus, putamen and claustrum. Cerebrospinal fluid lactate and pyruvate concentrations were in their normal ranges. Necropsy and histological examination confirmed the MRI findings as well as neuronal degeneration of the cerebellar cortex in the vermis and degenerative changes in the neocortex at the depths of the cerebral sulci. In view of the similarity of lesions to subacute necrotising encephalomyelopathy, known as Leigh's disease in humans, a tentative diagnosis of a mitochondrial encephalopathy was made.
MINOR MESH HEADINGS: Cerebellar-Cortex-pathology; Disease-Progression; Dogs-; Leigh-Disease-pathology; Magnetic-Resonance-Imaging; Mitochondrial-Encephalomyopathies-pathology
MAJOR MeSH HEADINGS: *Dog-Diseases-pathology; *Leigh-Disease-veterinary; *Mitochondrial-Encephalomyopathies-veterinary
Record 2 of 45 in MEDLINE EXPRESS (R) 2000/01-2000/05
TITLE: Clinical and molecular studies in three Portuguese mtDNA T8993G families.
AUTHOR(S): Vilarinho-L; Leao-E; Barbot-C; Santos-M; Rocha-H; Santorelli-FM
ADDRESS OF AUTHOR: Department of Clinical Biology, Instituto de Genetica Medica, Porto, Portugal.
SOURCE (BIBLIOGRAPHIC CITATION): Pediatr-Neurol. 2000 Jan; 22(1): 29-32
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: The T8993G mutation in the mitochondrial DNA adenosine triphosphatase 6 gene represents an important cause of maternally inherited Leigh's syndrome. Reported are the clinical findings and mutational loads in three Portuguese T8993G pedigrees. Polymerase chain reaction-restriction fragment length polymorphism analyses demonstrated the T8993G mutation in a high percentage of tissues from all patients (97% +/- 2.3%), but it was less abundant in the blood from 14 maternal relatives. The disease progressed severely in the probands but did not have the fatal course reported by others. To test whether this prolonged course was related to the presence of a specific, disease-associated haplogroup the origin of the mutational event in Portugal was traced. Haplotype investigation revealed an independent occurrence of the mutation in the three probands. These analyses represent the first molecular characterization of Portuguese patients with Leigh's syndrome.
MINOR MESH HEADINGS: Atrophy-; Basal-Ganglia-pathology; Child-; Child,-Preschool; Gene-Frequency; Haplotypes-; Leigh-Disease-pathology; Magnetic-Resonance-Imaging; Pedigree-; Portugal-
MAJOR MeSH HEADINGS: *Adenosinetriphosphatase-genetics; *DNA,-Mitochondrial-analysis; *Family-Health; *Leigh-Disease-genetics; *Point-Mutation
NAME OF SUBSTANCE: Adenosinetriphosphatase; DNA,-Mitochondrial
Record 3 of 45 in MEDLINE EXPRESS (R) 2000/01-2000/05
TITLE: Complex approach to prenatal diagnosis of cytochrome c oxidase deficiencies.
AUTHOR(S): Houstek-J; Klement-P; Hermanska-J; Antonicka-H; Houstkova-H; Stratilova-L; Wanders-RJ; Zeman-J
ADDRESS OF AUTHOR: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague. houstek@biomed.cas.cz
SOURCE (BIBLIOGRAPHIC CITATION): Prenat-Diagn. 1999 Jun; 19(6): 552-8
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: Different severe disorders of cytochrome c oxidase (COX) have been described in children, but only the defects with autosomal inheritance are suitable for prenatal diagnosis. To perform prenatal diagnosis of fatal infantile COX deficiency a complex approach has been used which combined determination of the genetic origin of the defect, and detailed analysis of the function, content and subunit composition of the enzyme in cultured fetal cells. The tissues and cultured fibroblasts of the patient with Leigh's syndrome showed a COX deficiency of systemic character. The decrease of COX activity to 5-11 per cent was accompanied by proportionally decreased content of the assembled COX enzyme. With the help of transmitochondrial cybrids derived from patient fibroblasts it was proven that the COX defect was of nuclear origin. In a successive pregnancy, the function of oxidative phosphorylation (OXPHOS) was analysed in cultured amniocytes by substrate-stimulated ATP production and COX activity was compared with the activity of citrate synthase. The amount and composition of OXPHOS complexes was estimated by two-dimensional (Blue Native/SDS) polyacrylamide gel electrophoresis and was verified immunochemically with specific antibodies. Three independent lines of evidence provided us with reliable data on the function of COX and OXPHOS in fetal cells which were sufficient to rule out the expected enzymatic defect within three weeks after amniocentesis.
MINOR MESH HEADINGS: Adenosine-Triphosphate-biosynthesis; Amniotic-Fluid-cytology; Cell-Nucleus-genetics; Cells,-Cultured; Child,-Preschool; Citrate-si-Synthase-metabolism; Cytochrome-c-Oxidase-metabolism; DNA,-Mitochondrial-genetics; DNA,-Mitochondrial-metabolism; Electrophoresis,-Gel,-Two-Dimensional; Fatal-Outcome; Hybrid-Cells; Mutation-; Oxidative-Phosphorylation; Pregnancy-
MAJOR MeSH HEADINGS: *Cytochrome-c-Oxidase-deficiency; *Prenatal-Diagnosis-methods
NAME OF SUBSTANCE: Cytochrome-c-Oxidase; Citrate-(si)-Synthase; DNA,-Mitochondrial; Adenosine-Triphosphate
Record 4 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Uncommon morphologic characteristics in Leigh's disease.
AUTHOR(S): Warmuth-Metz-M; Hofmann-E; Busse-M; Solymosi-L
ADDRESS OF AUTHOR: Department of Neuroradiology, University of Wurzburg, Germany.
SOURCE (BIBLIOGRAPHIC CITATION): AJNR-Am-J-Neuroradiol. 1999 Jun-Jul; 20(6): 1158-60
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: We describe a 4-month-old male patient with severe developmental delay and elevated lactate in blood and CSF. The MR images showed abnormalities differing from the typical pattern found in association with Leigh's disease. The examination of fibroblast cultures showed diminished activity of mitochondrial complexes I and III. The patient died at the age of 9 months.
MINOR MESH HEADINGS: Developmental-Disabilities-complications; Fatal-Outcome; Fibroblasts-enzymology; Infant-; Lactic-Acid-blood; Lactic-Acid-cerebrospinal-fluid; Leigh-Disease-complications; Leigh-Disease-metabolism; Magnetic-Resonance-Imaging; Mitochondria-enzymology; Multienzyme-Complexes-metabolism; NADPH-Dehydrogenase-Quinone-metabolism; Oxidoreductases-metabolism; Psychomotor-Disorders-complications; Succinate-Dehydrogenase-metabolism
MAJOR MeSH HEADINGS: *Leigh-Disease-diagnosis
NAME OF SUBSTANCE: Oxidoreductases; succinate-dehydrogenase-(ubiquinone); Succinate-Dehydrogenase; NAD(P)H-Dehydrogenase-(Quinone); Multienzyme-Complexes; Lactic-Acid
Record 5 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Oligomycin induces a decrease in the cellular content of a pathogenic mutation in the human mitochondrial ATPase 6 gene.
AUTHOR(S): Manfredi-G; Gupta-N; Vazquez-Memije-ME; Sadlock-JE; Spinazzola-A; De-Vivo-DC; Schon-EA
ADDRESS OF AUTHOR: Department of Neurology, H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. gm73@columbia.edu
SOURCE (BIBLIOGRAPHIC CITATION): J-Biol-Chem. 1999 Apr 2; 274(14): 9386-91
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: A T --> G mutation at position 8993 in human mitochondrial DNA is associated with the syndrome neuropathy, ataxia, and retinitis pigmentosa and with a maternally inherited form of Leigh's syndrome. The mutation substitutes an arginine for a leucine at amino acid position 156 in ATPase 6, a component of the F0 portion of the mitochondrial ATP synthase complex. Fibroblasts harboring high levels of the T8993G mutation have decreased ATP synthesis activity, but do not display any growth defect under standard culture conditions. Combining the notions that cells with respiratory chain defects grow poorly in medium containing galactose as the major carbon source, and that resistance to oligomycin, a mitochondrial inhibitor, is associated with mutations in the ATPase 6 gene in the same transmembrane domain where the T8993G amino acid substitution is located, we created selective culture conditions using galactose and oligomycin that elicited a pathological phenotype in T8993G cells and that allowed for the rapid selection of wild-type over T8993G mutant cells. We then generated cytoplasmic hybrid clones containing heteroplasmic levels of the T8993G mutation, and showed that selection in galactose-oligomycin caused a significant increase in the fraction of wild-type molecules (from 16 to 28%) in these cells.
MINOR MESH HEADINGS: Adenosinetriphosphatase-metabolism; Amino-Acid-Sequence; Cell-Line; Culture-; CHO-Cells; DNA,-Mitochondrial-chemistry; Fibroblasts-enzymology; Galactose-metabolism; Hamsters-; Molecular-Sequence-Data; Oxidative-Phosphorylation-Coupling-Factors-metabolism; Polymorphism,-Restriction-Fragment-Length
MAJOR MeSH HEADINGS: *Adenosinetriphosphatase-genetics; *DNA,-Mitochondrial-metabolism; *Mutation-; *Oligomycins-pharmacology; *Oxidative-Phosphorylation-Coupling-Factors-genetics
NAME OF SUBSTANCE: F(6)-ATPase; Adenosinetriphosphatase; DNA,-Mitochondrial; Oligomycins; Oxidative-Phosphorylation-Coupling-Factors; Galactose
Record 6 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: [Classification of mitochondrial diseases]
ORIGINAL TITLE: Clasificacion de las enfermedades mitocondriales.
AUTHOR(S): Lopez-de-Munain-A
ADDRESS OF AUTHOR: Servicio de Neurologia, Hospital Ntra. Sra. de Aranzazu, San Sebastian, Espana.
SOURCE (BIBLIOGRAPHIC CITATION): Rev-Neurol. 1998 Apr; 26 Suppl 1: S9-14
LANGUAGE OF ARTICLE: SPANISH; NON-ENGLISH
COUNTRY OF PUBLICATION: SPAIN
ABSTRACT: Clinical and biochemical classifications of mitochondrial disorders have given way to an as yet incomplete genetic classification system based on alterations of the mitochondrial genome, the nuclear genome, or both. The first group includes mitochondrial disorders due to specific mutations of mitochondrial DNA such as the MELAS, MERRF or NARP encephalomyopathies, various conditions involving deafness (non-syndromic or associated with diabetes), Leber's optic neuropathy and a small group of cases of maternally transmitted Leigh's syndrome. All these diseases are transmitted through maternal line. conditions which are usually sporadic are due to deletion or duplication of mitochondrial DNA, and give rise to myopathies, with or without ophthalmoplegia, and to more complex disorders such as Kearns Sayre syndrome are also included. The second group is composed of all the mitochondrial disorders in which the nuclear genes which codify sub-units of mitochondrial DNA contain a genetic defect. This includes most cases of Leigh's syndrome, Alpers polydystrophies, the myoneurogastrointestinal syndrome, Barth's syndrome and Friedreich's disease. Amongst the disorders secondary to defects in communication between the nuclear and mitochondrial genomes is a progressive external ophthalmoplegic form with autosomal dominance which arises secondary to mutations on chromosomes 3 and 10. Further mitochondrial disorders due to faults in the relationship between the two genomes will probably be found in the near future.
MINOR MESH HEADINGS: DNA,-Mitochondrial-genetics; English-Abstract; Mitochondrial-Myopathies-genetics
MAJOR MeSH HEADINGS: *Mitochondrial-Myopathies-classification
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 7 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Clinical and laboratory findings in referrals for mitochondrial DNA analysis [see comments]
COMMENTS: Comment in: Arch Dis Child 1999 Apr;80(4):398-9
AUTHOR(S): Lamont-PJ; Surtees-R; Woodward-CE; Leonard-JV; Wood-NW; Harding-AE
ADDRESS OF AUTHOR: Neurogenetics Section, Institute of Neurology, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Arch-Dis-Child. 1998 Jul; 79(1): 22-7
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: BACKGROUND: Increasingly, mutations of mitochondrial DNA (mtDNA) are being considered when investigating the aetiology of neurological diseases in childhood. However, they are often difficult to predict clinically. METHOD: Mitochondrial DNA analysis was carried out on 190 children from 1992 to 1996. Most patients were screened for large scale rearrangements and point mutations at nucleotide positions 3243, 3271, 8344, and 8993. RESULTS: Mutations were found in only 15 patients (7.9%) and were either large scale rearrangements (seven patients) or point mutations at nucleotide position 3243 (eight patients). Other point mutations were screened for depending on the clinical picture. The age of symptom onset was significantly older in children with an mtDNA mutation (mean 7.0 years) compared with children without a mutation (mean 2.8 years). Neither Leigh's syndrome (28 cases) nor severe infantile lactic acidosis (12 cases) was associated with mtDNA mutation. Only three clinical features were significantly associated with an mtDNA mutation: progressive external ophthalmoplegia, myopathy, and pigmentary retinopathy. Family history was valuable: the point mutation at nucleotide 3243 (but not the large scale rearrangements) was associated with maternal inheritance; and consanguinity was not associated with mtDNA mutations. The only investigation that provided specific evidence of an underlying mtDNA mutation was histochemical staining of muscle biopsy specimens. The large scale mutations associated with Kearns-Sayre syndrome and progressive external ophthalmoplegia were found in DNA from muscle only, not leucocyte DNA; whereas point mutations were found in leucocyte DNA. CONCLUSIONS: Even among children seen at a neurogenetic referral centre, mtDNA mutations were very uncommon. Muscle biopsy was the only investigation to provide evidence of mtDNA abnormality.
MINOR MESH HEADINGS: Acidosis,-Lactic-complications; Acidosis,-Lactic-genetics; Adolescence-; Age-of-Onset; Cerebrovascular-Disorders-genetics; Child-; Child,-Preschool; Genotype-; Infant-; Kearns-Syndrome-genetics; Leigh-Disease-genetics; Leukocytes-physiology; Mitochondria,-Muscle-genetics; Nervous-System-Diseases-complications; Nervous-System-Diseases-diagnosis; Phenotype-; Retrospective-Studies
MAJOR MeSH HEADINGS: *DNA-Mutational-Analysis; *DNA,-Mitochondrial; *Gene-Rearrangement; *Nervous-System-Diseases-genetics; *Point-Mutation
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 8 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Confirmation that a T-to-C mutation at 9176 in mitochondrial DNA is an additional candidate mutation for Leigh's syndrome.
AUTHOR(S): Makino-M; Horai-S; Goto-Y; Nonaka-I
ADDRESS OF AUTHOR: Department of Laboratory Medicine, National Center Hospital for Mental, Nervous and Muscular Disorders, Tokyo, Japan.
SOURCE (BIBLIOGRAPHIC CITATION): Neuromuscul-Disord. 1998 May; 8(3-4): 149-51
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: Among 80 patients with the clinical and brain imaging characteristics of Leigh's syndrome, 11 patients had a well-known mutation at nucleotide position (nt) 8993 in mitochondrial DNA. In addition, three patients had a T-to-C mutation at nt 9176 which had been described previously in only two brothers with bilateral striatal necrosis and one patient with Leigh's syndrome. In our three patients, one had the typical clinical characteristics of Leigh's syndrome from early infancy, and two had the later onset of neurological deficits. All had a slowly progressive course and basal ganglia abnormalities by neuroimaging. As nt 8993 and 9176 are located in the ATPase 6 coding region, altered ATPase function may be one of the enzyme abnormalities in Leigh's syndrome and other similar conditions with bilateral striatal necrosis.
MINOR MESH HEADINGS: Adolescence-; Amino-Acid-Sequence; Base-Sequence; Child-; Leigh-Disease-physiopathology
MAJOR MeSH HEADINGS: *DNA,-Mitochondrial-genetics; *Leigh-Disease-genetics; *Mutation-genetics
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 9 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Recent developments in the molecular genetics of mitochondrial disorders.
AUTHOR(S): Graeber-MB; Muller-U
ADDRESS OF AUTHOR: Department of Neuromorphology, Max-Planck-Institute of Psychiatry, Martinsried, Germany. neuropat@neuro.mpg.de
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurol-Sci. 1998 Jan 8; 153(2): 251-63
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: Rapid progress has been made in the identification of mitochondrial DNA mutations which are typically associated with diseases of the nervous system and muscle. The well established mitochondrial disorders are maternally inherited and males and females are equally affected. An exception is Leber's hereditary optic atrophy (LHON) which is observed much more frequently in males than in females. There are three common point mutations in LHON which can be homoplasmic or heteroplasmic. In mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) most mutations are single base changes and lie within the tRNA-Leu gene. Point mutations in myoclonic epilepsy with ragged red fibres (MERRF) usually occur within the tRNA-Lys gene but mutations of the tRNA-Leu gene are also observed. MELAS and MERRF mutations are heteroplasmic and there is considerable clinical overlap between these diseases. Point mutations within the ATPase6 gene result in either neuropathy, ataxia and retinitis pigmentosa (NARP) or in Leigh's syndrome. The latter occurs if the mutation is present in the majority of mitochondria (extreme heteroplasmy). Finally, mitochondrial DNA deletions are the cause underlying Kearns-Sayre syndrome (KSS). Apart from the well-established mitochondrial diseases, there is increasing evidence that mitochondrial mutations may also play a role in the neurodegenerative disorders Parkinson, Alzheimer and Huntington disease. The complex I defect found in Parkinson disease is especially interesting in this respect. However, no causative mitochondrial mutation has as yet been established in any of these three common disorders.
MAJOR MeSH HEADINGS: *Genetics,-Biochemical; *Mitochondria-physiology; *Mitochondrial-Encephalomyopathies-genetics; *Nerve-Degeneration-genetics; *Nerve-Degeneration-physiopathology
Record 10 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase [see comments]
COMMENTS: Comment in: Nat Genet 1998 Feb;18(2):99-100
AUTHOR(S): Melov-S; Schneider-JA; Day-BJ; Hinerfeld-D; Coskun-P; Mirra-SS; Crapo-JD; Wallace-DC
ADDRESS OF AUTHOR: Center for Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Nat-Genet. 1998 Feb; 18(2): 159-63
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Reactive oxygen species (ROS) have been implicated in a wide range of degenerative processes including amyotrophic lateral sclerosis, ischemic heart disease, Alzheimer disease, Parkinson disease and aging. ROS are generated by mitochondria as the toxic by-products of oxidative phosphorylation, their energy generating pathway. Genetic inactivation of the mitochondrial form of superoxide dismutase in mice results in dilated cardiomyopathy, hepatic lipid accumulation and early neonatal death. We report that treatment with the superoxide dismutase (SOD) mimetic Manganese 5, 10, 15, 20-tetrakis (4-benzoic acid) porphyrin (MnTBAP) rescues these Sod2tm1Cje(-/-) mutant mice from this systemic pathology and dramatically prolongs their survival. The animals instead develop a pronounced movement disorder progressing to total debilitation by three weeks of age. Neuropathologic evaluation reveals a striking spongiform degeneration of the cortex and specific brain stem nuclei associated with gliosis and intramyelinic vacuolization similar to that observed in cytotoxic edema and disorders associated with mitochondrial abnormalities such as Leighs disease and Canavans disease. We believe that due to the failure of MnTBAP to cross the blood brain barrier progressive neuropathology is caused by excessive mitochondrial production of ROS. Consequently, MnTBAP-treated Sod2tm1Cje(-/-) mice may provide an excellent model for examining the relationship between free radicals and neurodegenerative diseases and for screening new drugs to treat these disorders.
MINOR MESH HEADINGS: Brain-pathology; Brain-Stem-pathology; Brain-Stem-ultrastructure; Cerebral-Cortex-pathology; Cerebral-Cortex-ultrastructure; Free-Radical-Scavengers-pharmacology; Lipids-metabolism; Liver-metabolism; Mice-; Mice,-Knockout; Mitochondria-enzymology; Neurodegenerative-Diseases-drug-therapy; Neurodegenerative-Diseases-pathology; Neurons-pathology; Survival-Rate; Trigeminal-Nuclei-pathology; Trigeminal-Nuclei-ultrastructure; Vacuoles-pathology; Vacuoles-ultrastructure
MAJOR MeSH HEADINGS: *DNA,-Mitochondrial-genetics; *Metalloporphyrins-pharmacology; *Neurodegenerative-Diseases-genetics; *Superoxide-Dismutase-deficiency; *Superoxide-Dismutase-genetics
NAME OF SUBSTANCE: Superoxide-Dismutase; manganese(III)-tetrakis(4-benzoic-acid)porphyrin; DNA,-Mitochondrial; Free-Radical-Scavengers; Lipids; Metalloporphyrins
Record 11 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Anaesthetic management of a patient with Leigh's syndrome.
AUTHOR(S): Shenkman-Z; Krichevski-I; Elpeleg-ON; Joseph-A; Kadari-A
ADDRESS OF AUTHOR: Department of Anesthesiology and CCM, Hadassah University Hospital, Jerusalem, Israel.
SOURCE (BIBLIOGRAPHIC CITATION): Can-J-Anaesth. 1997 Oct; 44(10): 1091-5
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: CANADA
ABSTRACT: PURPOSE: Leigh's syndrome, a progressive neurodegenerative disorder of infancy and childhood, is clinically characterized mainly by developmental delay, nervous system dysfunction and respiratory abnormalities such as aspiration, wheezing, breathing difficulties, gasping, hypoventilation and apnoea. Acute exacerbation and respiratory failure may follow surgery, general anaesthesia or intercurrent illnesses. Hyperlecithinemia is variably present. Histopathological findings include necrosis, vascular proliferation, astrocytosis and demyelination of several brain areas. We present a 30-month-old patient with Leigh's syndrome anaesthetized for extracorporeal shockwave lithotripsy, and describe the anaesthetic considerations. CLINICAL FEATURES: Leigh's syndrome was diagnosed at five months of age based on failure to thrive, lethargy, hypotonicity, choreo-athetosis and lactic acidaemia, with basal ganglia hypodense areas demonstrated by brain computerized tomographic scan. Muscle pyruvate dehydrogenase complex and NADH coenzyme Q oxidoreductase activity were 25% and 13% of control. No preoperative respiratory symptoms or signs were present. Preoperative fasting lasted two hours and gastric aspiration was negative. Anaesthesia was induced with ketamine and midazolam im, and N2O in oxygen, and maintained with propotol and N2O. No volatile anaesthetics were used. Intravenous fluids given were 1/2 normal saline and glucose 5% administered. Besides laryngospasm during anaesthetic induction, relieved by sublingual succinylcholine injection, the perianaesthetic course was uneventful. The lungs were mechanically ventilated and lithotripsy was performed. No adverse sequelae have occurred, and the patient was discharged one day later. CONCLUSION: Perioperative management of patients with Leigh's syndrome requires cautious attention to the metabolic, neurological and respiratory aspects of the disease, and appropriate selection of anaesthetic drugs.
MINOR MESH HEADINGS: Child,-Preschool; Leigh-Disease-physiopathology; Lithotripsy-; Monitoring,-Intraoperative; Ureteral-Calculi-therapy
MAJOR MeSH HEADINGS: *Anesthesia,-General; *Leigh-Disease-complications
Record 12 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Movement disorders and mitochondrial dysfunction.
AUTHOR(S): Hanna-MG; Bhatia-KP
ADDRESS OF AUTHOR: Neurogenetics Section, University Department of Clinical Neurology, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Curr-Opin-Neurol. 1997 Aug; 10(4): 351-6
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Primary defects of mitochondrial DNA leading to respiratory chain dysfunction have been described in association with dystonia, chorea and parkinsonism. Myoclonus remains the commonest movement disorder associated with such defects. The genetic basis of Leigh's syndrome, which is frequently associated with movement disorders, may be mitochondrial or nuclear. Respiratory chain dysfunction has been identified in Huntington's disease in addition to Parkinson's disease, but the cause and relationship of this dysfunction to the pathogenesis of these common disorders is not yet determined.
MINOR MESH HEADINGS: Chorea-genetics; Dystonia-genetics; Myoclonus-genetics; Parkinson-Disease-genetics
MAJOR MeSH HEADINGS: *Mitochondrial-Encephalomyopathies-physiopathology; *Movement-Disorders-genetics
Record 13 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Subacute necrotizing encephalomyelopathy (Leigh's disease): a clinicopathologic study of ten cases.
AUTHOR(S): Agapitos-E; Pavlopoulos-PM; Patsouris-E; Davaris-P
ADDRESS OF AUTHOR: Department of Pathology, Medical School, National University of Athens, Greece.
SOURCE (BIBLIOGRAPHIC CITATION): Gen-Diagn-Pathol. 1997 Jun; 142(5-6): 335-41
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: GERMANY
ABSTRACT: Archival material and clinical data of 10 autopsy cases of Leigh's disease (LS), aged from 44 days to 9 years at death, were reviewed. Development delay, irregular respiration, feeding difficulty, and abnormal eye signs were the most common symptoms. Seizures (five of ten cases) were also frequent. In most patients, the diagnosis of LS was established postmortemly by the presence of symmetrical spongiform lesions affecting several brain centers at autopsy. The histologic examination disclosed associated hypertrophic cardiomyopathy in six cases, while fatty infiltration of the hepatocytes was observed in four cases. Microvesicular degeneration of the renal tubular epithelial cells was also seen in four cases. Our observations suggest that liver and kidney involvement is a component of LS and that this rare entity has to be considered as a polysystematic disorder, able to affect other organs besides the nervous system and the heart, a fact which has not been emphasized enough in the existing literature.
MINOR MESH HEADINGS: Autopsy-; Brain-pathology; Child-; Child,-Preschool; Infant-; Myocardium-pathology
MAJOR MeSH HEADINGS: *Kidney-pathology; *Leigh-Disease-pathology; *Liver-pathology
Record 14 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Late onset familial dystonia: could mitochondrial deficits induce a diffuse lesioning process of the whole basal ganglia system?
AUTHOR(S): Caparros-Lefebvre-D; Destee-A; Petit-H
ADDRESS OF AUTHOR: Department of Neurology, CHU Pointe a Pitre, Guadeloupe, French West Indies, France.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurol-Neurosurg-Psychiatry. 1997 Aug; 63(2): 196-203
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: BACKGROUND: Striatal necrosis has been related to various clinical syndromes, with acute or chronic progression, and juvenile or late occurrence, but the most common type is Leigh's encephalopathy. METHODS: Between 1967 and 1995, six out of seven related patients with chronic familial dystonia were examined. MRIs were performed in four, between 1992-1994. The seven members, affected over three generations, were the father, three daughters (one surviving), and three surviving grandsons. RESULTS: The leading symptoms were gait disorders and dystonia in all, dysarthria in six, verbal and motor stereotypies in two, and parkinsonian and cerebellar signs in three. Optic neuropathy was found in three. A frontal lobe syndrome without amnesia occurred in two. Symptoms occurred between the second and the fifth decade, with progressive deterioration. Magnetic resonance imaging, performed in four, showed in the two patients with severe neurological signs diffuse striatopallidal abnormal hyposignal (comparable with CSF signal) in T1 weighted images, suggesting extensive necrosis of the striatum and pallidum, associated with thalamo-subthalamo-rubro-dentato-nigral and substantia innominata hypersignals in T2 weighted images suggesting gliosis in these respective areas. The same images were described to a lesser extent in a third patient. Concentrations of lactate in CSF and serum were normal in three. Muscle biopsy, performed in four, was shown to be normal. Enzyme histochemistry showed complex I, III, and IV deficiency in surviving patients. CONCLUSION: This familial dystonia of chronic progression may be related to basal ganglia necrosis or gliosis, associated with alterations in the respiratory chain. These metabolic alterations probably play a part in the pathophysiology of these unusual brain lesions.
MINOR MESH HEADINGS: Cytochrome-c-Oxidase-deficiency; Dystonia-enzymology; DNA,-Mitochondrial-genetics; Magnetic-Resonance-Imaging; NADPH-Dehydrogenase-Quinone-deficiency; Pedigree-; Retrospective-Studies; Succinate-Cytochrome-c-Oxidoreductase-deficiency
MAJOR MeSH HEADINGS: *Basal-Ganglia-pathology; *Dystonia-genetics; *Dystonia-pathology
NAME OF SUBSTANCE: Succinate-Cytochrome-c-Oxidoreductase; NAD(P)H-Dehydrogenase-(Quinone); Cytochrome-c-Oxidase; DNA,-Mitochondrial
Record 15 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin.
AUTHOR(S): Armstrong-RW; Steinbok-P; Cochrane-DD; Kube-SD; Fife-SE; Farrell-K
ADDRESS OF AUTHOR: Department of Paediatrics, University of British Columbia, British Columbia's Children's Hospital, and Sunny Hill Health Centre for Children, Vancouver, Canada.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurosurg. 1997 Sep; 87(3): 409-14
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Management of severe spasticity in children is often a difficult problem. Orally administered medications generally offer limited benefits. This study examines the value of intrathecally administered baclofen in the treatment of 19 children with severe spasticity of cerebral origin: eight of whom sustained brain injury associated with trauma, near drowning, or cardiac arrest; 10 with cerebral palsy (spastic quadriplegia); and one child with Leigh's disease. At the time of entry into the study, patients ranged from 4 to 19 years of age, and all were completely dependent on caretakers for activities of daily living. Children who responded positively to a trial dose of intrathecal baclofen underwent insertion of a drug delivery system for continuous infusion. This was followed by a double-blind trial of baclofen or placebo and follow-up review at 3 and 6 months, and yearly thereafter. Seven children did not undergo pump implantation because of excess sedation or poor response. The 12 remaining children have been followed for a period of 1 to 5 years. Favorable responses were present in all 12 children as determined by the Ashworth Scale, with the greatest benefit being reduction of lower limb tone. Except in the case of one child who had reduction in lower limb tone that resulted in difficulty with transfers, the caretakers all reported significant benefits from intrathecal baclofen, with improvement in muscle tone, behavior, sitting, and general ease of care being most commonly noted. Central side effects were seen in some children who received continuous intrathecal baclofen infusion and included hypotension (two patients), bradycardia (two), apnea or respiratory depression (two), and sedation (one). During a total of 568 months of pump operation there were 10 mechanical complications, including two related to pump or side port failure and eight related to catheter kinks, extrusions, or dislodgment. Pump pocket effusion occurred in five children and a cerebrospinal fluid fistula was seen in one child. Local infection occurred in three children and meningitis in two children. The results demonstrate the potential value of continuous intrathecal baclofen infusion for treatment of severe spasticity of cerebral origin. However, this treatment can result in significant complications and more experience is required before the long-term benefits can be determined.
MINOR MESH HEADINGS: Adolescence-; Baclofen-administration-and-dosage; Baclofen-adverse-effects; Child-; Child,-Preschool; Infusion-Pumps,-Implantable-adverse-effects; Infusions,-Parenteral-methods; Injections,-Spinal-methods; Muscle-Relaxants,-Central-administration-and-dosage; Muscle-Relaxants,-Central-adverse-effects; Muscle-Spasticity-etiology; Treatment-Outcome
MAJOR MeSH HEADINGS: *Baclofen-therapeutic-use; *Brain-Injuries-complications; *Cerebral-Palsy-complications; *Muscle-Relaxants,-Central-therapeutic-use; *Muscle-Spasticity-drug-therapy
NAME OF SUBSTANCE: Muscle-Relaxants,-Central; Baclofen
Record 16 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: A single cell complementation class is common to several cases of cytochrome c oxidase-defective Leigh's syndrome.
AUTHOR(S): Munaro-M; Tiranti-V; Sandona-D; Lamantea-E; Uziel-G; Bisson-R; Zeviani-M
ADDRESS OF AUTHOR: Division of Biochemistry and Genetics, National Neurological Institute, C. Besta, Milan, Italy.
SOURCE (BIBLIOGRAPHIC CITATION): Hum-Mol-Genet. 1997 Feb; 6(2): 221-8
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: A generalized defect of complex IV (cytochrome C oxidase, COX) is frequently found in subacute necrotizing encephalomyelopathy (Leigh's syndrome), the most common mitochondrial disorder in infancy. We previously demonstrated the nuclear origin of the COX defect in one case, by fusing nuclear DNA-less cytoplasts derived from normal fibroblasts with mitochondrial DNA (mtDNA)-less transformant fibroblasts derived from a patient with COX-defective [COX(-)] Leigh's syndrome. The resulting cybrid line showed a specific and serve COX(-) phenotype. Conversely, in the present study, we demonstrated that a COX(+) phenotype could be restored in hybrids obtained by fusing COX(-) transformant fibroblasts of seven additional Leigh's syndrome patients with mtDNA-less, COX(-) tumor-derived rho degree cells. Both these results are explained by the presence of a mutation in a nuclear gene. In a second set of experiments, in order to demonstrate whether COX(-) Leigh's syndrome is due to a defect in the same gene, or in different genes, we tested several hybrids derived by fusing our original COX(-) cell line with each of the remaining seven cell lines. COX activity was evaluated in situ by histochemical techniques and in cell extracts by a spectrophotometric assay. No COX complementers were found among the resulting hybrid lines. This result demonstrates that all our cases were genetically homogeneous, and suggests that a major nuclear disease locus is associated with several, perhaps most, of the cases of infantile COX(-) Leigh's syndrome. This information should make it easier to identify the gene responsible.
MINOR MESH HEADINGS: Cell-Fusion; Cell-Line; Child-; Child,-Preschool; Cytochrome-c-Oxidase-genetics; Electron-Transport; Genetic-Complementation-Test; Genotype-; Leigh-Disease-genetics; Succinate-Dehydrogenase-metabolism; Syndrome-
MAJOR MeSH HEADINGS: *Cytochrome-c-Oxidase-metabolism; *Leigh-Disease-enzymology
NAME OF SUBSTANCE: Succinate-Dehydrogenase; Cytochrome-c-Oxidase
Record 17 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Mitochondrial disease associated with the T8993G mutation of the mitochondrial ATPase 6 gene: a clinical, biochemical, and molecular study in six families.
AUTHOR(S): Uziel-G; Moroni-I; Lamantea-E; Fratta-GM; Ciceri-E; Carrara-F; Zeviani-M
ADDRESS OF AUTHOR: Division of Child Neurology, Istituto Nazionale Neurologico Carlo Besta, Milano, Italy.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurol-Neurosurg-Psychiatry. 1997 Jul; 63(1): 16-22
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: AIM: To contribute to the establishment of a rational clinical, neuroradiological, and molecular approach to neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and maternally inherited Leigh's syndrome (MILS). METHODS AND RESULTS: The T8993G mutation in the mitochondrial genome was found in several maternal members of six pedigrees, whose clinical status ranged from no symptoms to severe infantile subacute necrotising encephalomyelopathy (Leigh's disease). In one case a MELAS-like syndrome was documented both clinically and neuroradiologically. Relevant genetic features of the series were anticipation of symptoms through subsequent generations, and the presence of several cases in whom the mutation apparently occurred recently or was new. A uniform distribution of the mutation in many tissues was shown in one patient subjected to necropsy. In general, a good correlation was found between clinical severity and mutation heteroplasmy in readily accessible tissues, such as lymphocytes or fibroblasts. By contrast, a consistent reduction of the mitochondrial ATPase activity, to about half of the normal values, was found in most of the clinically affected cases, irrespective of the amount of mutant mitochondrial DNA. CONCLUSIONS: Although the measurement of ATP hydrolysis in cultured fibroblasts was a reliable, and sometimes instrumental, means to identify T8993G positive patients, the relation between the mutation and the oxidative phosphorylation defect is probably very complex, and its understanding requires more complex biochemical analysis.
MINOR MESH HEADINGS: Adenosinetriphosphatase-metabolism; Adult-; Age-of-Onset; Brain-pathology; Child-; Child,-Preschool; DNA-Mutational-Analysis; Genotype-; Infant-; Leigh-Disease-genetics; Leigh-Disease-metabolism; Magnetic-Resonance-Imaging; Mitochondrial-Encephalomyopathies-genetics; Mitochondrial-Encephalomyopathies-metabolism; MELAS-Syndrome-diagnosis; MELAS-Syndrome-genetics; Oxidative-Phosphorylation; Pedigree-; Phenotype-; Retinitis-Pigmentosa-diagnosis; Retinitis-Pigmentosa-genetics; Retinitis-Pigmentosa-metabolism; Severity-of-Illness-Index
MAJOR MeSH HEADINGS: *Adenosinetriphosphatase-genetics; *DNA,-Mitochondrial-genetics; *Leigh-Disease-diagnosis; *Mitochondria,-Muscle-enzymology; *Mitochondrial-Encephalomyopathies-diagnosis; *Mutation-
NAME OF SUBSTANCE: Adenosinetriphosphatase; DNA,-Mitochondrial
Record 18 of 45 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome.
AUTHOR(S): Adams-PL; Lightowlers-RN; Turnbull-DM
ADDRESS OF AUTHOR: Department of Neurology, University of Newcastle upon Tyne, United Kingdom.
SOURCE (BIBLIOGRAPHIC CITATION): Ann-Neurol. 1997 Feb; 41(2): 268-70
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Cytochrome c oxidase deficiency is the most common biochemical defect associated with Leigh's syndrome. The genetic defect responsible for this deficiency has not been identified in any patient with Leigh's syndrome. Given that this disorder appears to be inherited as an autosomal recessive trait, this would suggest prima facie that one of the nuclear DNA-encoded cytochrome c oxidase subunits is affected. We report the first detailed sequence analysis of all 10 cytochrome c oxidase nuclear complementary DNAs and the cytochrome c oxidase mitochondrial genes in a Leigh's syndrome patient with cytochrome c oxidase deficiency. No pathological mutations were identified in any of the cytochrome c oxidase structural genes.
MINOR MESH HEADINGS: Adult-; Base-Sequence; Molecular-Sequence-Data
MAJOR MeSH HEADINGS: *Cytochrome-c-Oxidase-metabolism; *Leigh-Disease-metabolism
NAME OF SUBSTANCE: Cytochrome-c-Oxidase
Record 19 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Progressive myoclonus epilepsy with focal brainstem degeneration and paternal inheritance. An autopsy report of 4 cases from 2 pedigrees.
AUTHOR(S): Moss-TH; Stevens-DL; Campbell-MJ
ADDRESS OF AUTHOR: Department of Neuropathology, Frenchay Hospital, Bristol, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Clin-Neuropathol. 1996 Mar-Apr; 15(2): 106-12
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: GERMANY
ABSTRACT: Four autopsied cases of myoclonus, ataxia, and epilepsy from 2 separate pedigrees are described. An identical pattern of focal brainstem lesions was found in all the cases with selective and symmetrical degeneration of the dentate and second order somatosensory nuclei. The combined clinical and pathological features did not appear to match any familial disorder previously described as causing progressive myoclonus epilepsy. Myoclonus epilepsy with ragged red fibres was excluded on the grounds of paternal inheritance and negative muscle biopsy findings, but the more acute lesions seen in 1 case are reminiscent of those found in Leigh's syndrome, and suggest that some other form of inherited defect of oxidative metabolism may be involved.
MINOR MESH HEADINGS: Cerebellar-Nuclei-pathology; Child-; Epilepsies,-Myoclonic-genetics; Pedigree-
MAJOR MeSH HEADINGS: *Brain-Stem-pathology; *Epilepsies,-Myoclonic-pathology; *Nerve-Degeneration
Record 20 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: [Leigh's encephalopathy (subacute necrotizing encephalopathy). Documentation of its evolution through neuroimaging]
ORIGINAL TITLE: Encefalopatia de Leigh (encefalopatia necrotizante subaguda). Documentacion de su evolucion por neuroimagen.
AUTHOR(S): Pena-JA; Gonzalez-Ferrer-S; Martinez-C; Prieto-Carrasquero-M; Delgado-W; Mora-La-Cruz-E
ADDRESS OF AUTHOR: Catedra de Clinica Pediatrica, Facultad de Medicina, Universidad del Zulia, Venezuela.
SOURCE (BIBLIOGRAPHIC CITATION): Invest-Clin. 1996 Sep; 37(3): 183-9
LANGUAGE OF ARTICLE: SPANISH; NON-ENGLISH
COUNTRY OF PUBLICATION: VENEZUELA
ABSTRACT: A 30 months-old boy developed bilateral nistagmus, tremor, gait disturbance, hypotonia and disartria. The diagnose of Leigh encephalopathy was suggested on the basis of clinical, neuroimaging and laboratory findings. Computed tomography and magnetic resonance imaging (MRI) at an early stage revealed bilateral and symmetric lesions in the putamen, appearing as hyperintense signal on T2-weighted images. Twelve months later a relatively large hypertense area in the posterior brainstem was observed. At this stage, the patient exhibited marked deterioration, dystonic manifestations, rigidity and respiratory disturbances. He died 6 months later for respiratory arrest during bronconeumonic infection. We believe MRI is a valuable means to allow assessment of the evolution of the disease.
MINOR MESH HEADINGS: Child,-Preschool; Diagnosis,-Differential; English-Abstract; Fatal-Outcome; Leigh-Disease-pathology; Putamen-pathology
MAJOR MeSH HEADINGS: *Leigh-Disease-diagnosis; *Magnetic-Resonance-Imaging
Record 21 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Mitochondrial NADH-coenzyme Q reductase deficiency in Leigh's disease.
AUTHOR(S): Huang-MY; Jong-YJ; Tsai-JL; Liu-GC; Chiang-CH; Pang-CY; Wei-YH
ADDRESS OF AUTHOR: Department of Pediatrics, Kaohsiung Medical College, Taiwan ROC.
SOURCE (BIBLIOGRAPHIC CITATION): J-Formos-Med-Assoc. 1996 Apr; 95(4): 325-8
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: TAIWAN
ABSTRACT: A 4 1/2-month-old girl suffered from psychomotor retardation, generalized hypotonia, poor feeding, hyperreflexia, nystagmus, optical atrophy and choreoathetosis from the age of 3 months. Her blood lactate level was elevated to 40 mg/dL. Magnetic resonance imaging of her brain showed low T1 and high T2 signal intensities in the bilateral putamen, thalamus, red nuclei, substantia nigra, superior and inferior colliculi, cerebral peduncles and periaqueductal lesions. Muscle histochemistry and electron microscopic examinations were all normal except for variation in fiber size showing a myopathic change. An assay of muscle mitochondrial respiratory enzyme activities revealed a deficiency of NADH-coenzyme Q reductase. Molecular analysis did not reveal the putative T to G transversion at the nucleotide 8,993 of mitochondrial DNA in muscle biopsies. Leigh's disease was indicated by the clinical and radiologic manifestations. The patient died at 10 months of age from pneumonia and respiratory failure. There have been only sporadic reports of patients with Leigh's disease in Taiwan, and, to our knowledge, this is the first documented case of a Taiwanese patient with mitochondrial NADH-coenzyme Q reductase deficiency.
MINOR MESH HEADINGS: Base-Sequence; Infant-; Molecular-Sequence-Data; NADH,-NADPH-Oxidoreductases-genetics
MAJOR MeSH HEADINGS: *Leigh-Disease-enzymology; *Mitochondria-enzymology; *NADH,-NADPH-Oxidoreductases-deficiency
NAME OF SUBSTANCE: NADH,-NADPH-Oxidoreductases; NADH-dehydrogenase-(ubiquinone)
Record 22 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.
AUTHOR(S): Pitkanen-S; Robinson-BH
ADDRESS OF AUTHOR: Department of Pediatrics, University of Toronto, Ontario, Canada.
SOURCE (BIBLIOGRAPHIC CITATION): J-Clin-Invest. 1996 Jul 15; 98(2): 345-51
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Mitochondria were isolated from skin fibroblast cultures derived from healthy individuals (controls) and from a group patients with complex I (NADH-CoQ reductase) deficiency of the mitochondrial respiratory chain. The complex I deficient patients included those with fatal infantile lactic acidosis (FILA), cardiomyopathy with cataracts (CC), hepatopathy with tubulopathy (HT), Leigh's disease (LD), cataracts and developmental delay (CD), and lactic acidemia in the neonatal period followed by mild symptoms (MS). Production of superoxide radicals, on addition of NADH, were measured using the luminometric probe lucigenin with isolated fibroblast mitochondrial membranes. Superoxide production rates were highest with CD and decreased in the order CD >> MS > LD > control > HT > FILA = CC. The quantity of Mn-superoxide dismutase (MnSOD), as measured by ELISA techniques, however, was highest in CC and FILA and lowest in CD. Plots of MnSOD quantity versus superoxide production showed an inverse relationship for most conditions with complex I deficiency. We hypothesize that oxygen radical production is increased when complex I activity is compromised. However, the observed superoxide production rates are modulated by the variant induction of MnSOD which decreases the rates, sometimes below those seen in control fibroblast mitochondria. In turn, we show that the variant induction of MnSOD is most likely a function of the change in the redox state of the cell experienced rather than a result of the complex I defect per se.
MINOR MESH HEADINGS: Cataract-enzymology; Cataract-genetics; Cells,-Cultured; Enzyme-Induction; Fibroblasts-metabolism; Infant-; Infant,-Newborn; Kinetics-; Lactates-metabolism; Leigh-Disease-enzymology; Leigh-Disease-genetics; Liver-Diseases-enzymology; Liver-Diseases-pathology; Metabolism,-Inborn-Errors-enzymology; Myocardial-Diseases-enzymology; Myocardial-Diseases-genetics; Reference-Values; Regression-Analysis
MAJOR MeSH HEADINGS: *Mitochondria-metabolism; *NADPH-Dehydrogenase-Quinone-deficiency; *Skin-metabolism; *Superoxide-Dismutase-biosynthesis; *Superoxides-metabolism
NAME OF SUBSTANCE: Superoxide-Dismutase; NAD(P)H-Dehydrogenase-(Quinone); Lactates; Superoxides
Record 23 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation.
AUTHOR(S): Shoffner-JM; Brown-MD; Stugard-C; Jun-AS; Pollock-S; Haas-RH; Kaufman-A; Koontz-D; Kim-Y; Graham-JR; et-al
ADDRESS OF AUTHOR: Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Ann-Neurol. 1995 Aug; 38(2): 163-9
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: A novel point mutation in the ND6 subunit of complex I at position 14,459 of the mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for the highly tissue-specific disease. Leber's hereditary optic neuropathy plus dystonia. Since the MTND6*LDYT14459A mutation was identified in a single family, other pedigrees with the mutation are needed to confirm its association with the disease. Clinical, biochemical, and genetic characterization is reported in two additional pedigrees. Leber's hereditary optic neuropathy developed in two family members in one pedigree. The daughter had clinically silent basal ganglia lesions. In a second pedigree, a single individual presented with childhood-onset generalized dystonia and bilateral basal ganglia lesions. Patient groups that included individuals with Leigh's disease, dystonia plus complex neurodegeneration, and Leber's hereditary optic neuropathy did not harbor the MTND6*LDYT14459A mutation, suggesting that this mutation displays a high degree of tissue specificity, thus producing a narrow phenotypic range. These results confirm the association of the MTND6*LDYT14459A mutation with Leber's hereditary optic neuropathy and/or dystonia. As the first genetic abnormality that has been identified to cause generalized dystonia, this mutation suggests that nuclear DNA or mitochondrial DNA mutations in oxidative phosphorylation genes are important considerations in the pathogenesis of dystonia.
MINOR MESH HEADINGS: Adolescence-; Adult-; Dystonia-enzymology; Middle-Age; Optic-Atrophies,-Hereditary-enzymology
MAJOR MeSH HEADINGS: *Dystonia-genetics; *DNA,-Mitochondrial-genetics; *Optic-Atrophies,-Hereditary-genetics; *Point-Mutation
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 24 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: [Adult Leigh syndrome. A rare differential diagnosis of central respiratory insufficiency]
ORIGINAL TITLE: Das adulte Leigh-Syndrom. Eine seltene Differentialdiagnose einer zentralen Atemregulationsstorung.
AUTHOR(S): Spranger-M; Schwab-S; Wiebel-M; Becker-CM
ADDRESS OF AUTHOR: Neurologische Klinik, Universitat Heidelberg.
SOURCE (BIBLIOGRAPHIC CITATION): Nervenarzt. 1995 Feb; 66(2): 144-9
LANGUAGE OF ARTICLE: GERMAN; NON-ENGLISH
COUNTRY OF PUBLICATION: GERMANY
ABSTRACT: Subacute necrotizing encephalomyelopathy (Leigh's syndrome) is a rare neurodegenerative disease in the adult. The precise metabolic defect is unknown, but abnormalities of a mitochondrial enzyme system related to cytochrome-c oxidase or pyruvate dehydrogenase are described. The clinical picture usually consists of an altered breathing pattern, oculomotor paralysis, other signs of cranial nerve dysfunction, ataxia, myoclonic jerks, nystagmus, generalized seizures, optic atrophy and demyelinating peripheral neuropathy. Hypopnea leads to CO2-retention with consecutive loss of consciousness demanding mechanical ventilation. Respiratory failure is the most frequent cause of death. Here we describe two patients with adult onset Leigh's syndrome and we discuss the longterm treatment strategies including vitamin B1 and CPAP mask.
MINOR MESH HEADINGS: Adult-; Cytochrome-c-Oxidase-deficiency; English-Abstract; Leigh-Disease-complications; Magnetic-Resonance-Imaging; Neurologic-Examination; Pyruvate-Dehydrogenase-Complex-Deficiency-Disease-complications; Pyruvate-Dehydrogenase-Complex-Deficiency-Disease-diagnosis; Respiratory-Insufficiency-diagnosis; Tegmentum-Mesencephali-pathology; Thalamic-Nuclei-pathology
MAJOR MeSH HEADINGS: *Leigh-Disease-diagnosis; *Respiratory-Insufficiency-etiology
NAME OF SUBSTANCE: Cytochrome-c-Oxidase
Record 25 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Leigh syndrome presenting with dystonia: report of one case.
AUTHOR(S): Huang-WY; Chi-CS; Mak-SC; Wu-HM; Yang-MT
ADDRESS OF AUTHOR: Department of Pediatrics, Kuang-Tien General Hospital, ShaLu, Taiwan, R.O.C.
SOURCE (BIBLIOGRAPHIC CITATION): Chung-Hua-Min-Kuo-Hsiao-Erh-Ko-I-Hsueh-Hui-Tsa-Chih. 1995 Sep-Oct; 36(5): 378-81
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: TAIWAN
ABSTRACT: A 22-month-old female presented with developmental delay and dystonia. The T2 weighted image of the brain MRI showed bilateral symmetrical high signal lesions over the putamen. An increased serum lactate pyruvate ratio (29.25) and a positive oral glucose lactate stimulation test were noted. Electron microscopic examination showed abnormal mitochondrial aggregation with band cristae in the subsarcolemmal area. These findings were indicative of clinical Leigh's syndrome. However, unusually the mt DNA analysis showed a point mutation at the nucleotide position 8344.
MINOR MESH HEADINGS: DNA,-Mitochondrial-genetics; Infant-; Leigh-Disease-genetics; Leigh-Disease-pathology; Point-Mutation
MAJOR MeSH HEADINGS: *Dystonia-etiology; *Leigh-Disease-diagnosis
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 26 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: The hippocampus in aging and Alzheimer's disease.
AUTHOR(S): de-Leon-MJ; Convit-A; DeSanti-S; Golomb-J; Tarshish-C; Rusinek-H; Bobinski-M; Ince-C; Miller-DC; Wisniewski-HM; et-al
ADDRESS OF AUTHOR: New York University Medical Center, New York, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Neuroimaging-Clin-N-Am. 1995 Feb; 5(1): 1-17
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: The role of imaging in the evaluation of neurodegenerative disorders is summarized. The primary role of imaging is to exclude potentially treatable disorders such as meningioma, extracerebral hematoma, Wernicke's disease, and hypothyroidism. Atrophic changes dominate in the hippocampal region on Alzheimer's disease versus the anterior, frontal, and temporal lobes in Pick's disease. Signal hypointensity in the putamen on T2-weighted spin-echo images favors poorly drug-responsive Parkinson's disease whereas putaminal hyperintensity is observed with Creutzfeldt-Jacob, Wilson's, and Leigh's diseases. As our population ages, a thorough understanding of imaging findings in a geriatric population assumes an increasing importance.
MINOR MESH HEADINGS: Aged-; Aged,-80-and-over; Atrophy-; Dementia-diagnosis; Diagnosis,-Differential; Parkinson-Disease-diagnosis; Putamen-pathology
MAJOR MeSH HEADINGS: *Aging-pathology; *Alzheimer-Disease-diagnosis; *Diagnostic-Imaging; *Hippocampus-pathology
Record 27 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Kearns-Sayre syndrome associated with mitochondrial DNA deletion or duplication: a molecular genetic and pathological study.
AUTHOR(S): Brockington-M; Alsanjari-N; Sweeney-MG; Morgan-Hughes-JA; Scaravilli-F; Harding-AE
ADDRESS OF AUTHOR: University Department of Clinical Neurology, Institute of Neurology, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurol-Sci. 1995 Jul; 131(1): 78-87
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: The neuropathological findings in 2 patients with Kearns-Sayre syndrome and mitochondrial DNA (mtDNA) rearrangements, one a predominant deletion and the other a predominant duplication, were remarkably similar, showing diffuse vacuolation of white matter. There were some of the pathological features of Leigh's syndrome in the spinal cord of the patient with a duplication. In the patient with a predominant deletion, rearranged mtDNA was undetectable in blood, spleen, and testis, and present in highest amounts in muscle and the brain, but relatively low in cerebellum, reflecting the ratio seen, albeit in much smaller amounts, in normal aged brains. MtDNA rearrangements in this patient were largely deletions or deletion dimers; duplicated mtDNA was present in only trace amounts in some tissues and there was none in skeletal muscle. The patient with a predominant duplication of mtDNA had higher amounts of rearranged mtDNA in blood (mainly duplicated) than muscle (mainly deleted). Correlation of these data with tissue dysfunction is probably complicated by the replicative behaviour of deleted, duplicated and normal mtDNA.
MINOR MESH HEADINGS: Adolescence-; Adult-; Basal-Ganglia-metabolism; Basal-Ganglia-pathology; Blotting,-Southern; Brain-pathology; Brain-Chemistry; DNA,-Mitochondrial-analysis; Kearns-Syndrome-pathology; Spinal-Cord-metabolism; Spinal-Cord-pathology
MAJOR MeSH HEADINGS: *DNA,-Mitochondrial-genetics; *Gene-Deletion; *Kearns-Syndrome-genetics; *Multigene-Family-physiology
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 28 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Mitochondrial defects in basal ganglia diseases.
AUTHOR(S): Shoffner-JM
ADDRESS OF AUTHOR: Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Curr-Opin-Neurol. 1995 Dec; 8(6): 474-9
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Mitochondrial DNA mutations are important causes of movement disorders and are often associated with basal ganglia degeneration. Leigh's disease and a form of generalized dystonia are caused by mitochondrial DNA mutations. Recent biochemical and genetic evidence suggests that some cases of Parkinson's disease may be caused by oxidative phosphorylation defects.
MINOR MESH HEADINGS: Movement-Disorders-metabolism; Oxidative-Phosphorylation
MAJOR MeSH HEADINGS: *Basal-Ganglia-Diseases-metabolism; *Mitochondria-metabolism
Record 29 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Nuclear DNA origin of cytochrome c oxidase deficiency in Leigh's syndrome: genetic evidence based on patient's-derived rho degrees transformants.
AUTHOR(S): Tiranti-V; Munaro-M; Sandona-D; Lamantea-E; Rimoldi-M; DiDonato-S; Bisson-R; Zeviani-M
ADDRESS OF AUTHOR: Division of Biochemistry and Genetics, Istituto Nazionale Neurologico Carlo Besta, Milano, Italy.
SOURCE (BIBLIOGRAPHIC CITATION): Hum-Mol-Genet. 1995 Nov; 4(11): 2017-23
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: Defects of the respiratory chain carrying out oxidative phosphorylation (OXPHOS) are the biochemical hallmark of human mitochondrial disorders. Faulty OXPHOS can be due to mutations in either nuclear or mitochondrial genes, that are involved in the synthesis of individual respiratory subunits or in their post-translational control. The most common mitochondrial disorder of infancy and childhood is Leigh's syndrome, a severe encephalopathy, often associated with a defect of cytochrome c oxidase (COX). In order to demonstrate which genome is primarily involved in COX-deficient (COX(-))-Leigh's syndrome, we generated two lines of transmitochondrial cybrids. The first was obtained by fusing nuclear DNA-less cytoplasts derived from normal fibroblasts, with mitochondrial DNA-less (rho degree) transformant fibroblasts derived from a patient with COX(-))-Leigh's syndrome. The second cybrid line was obtained by fusing rho degree cells derived from 143B.TK- human osteosarcoma cells, with cytoplasts derived from the same patient. The first cybrid line showed a specific and severe COX(-) phenotype, while in the second all the respiratory chain complexes, including COX, were normal. These results indicate that the COX defect in our patient is due to a mutation of a nuclear gene. The use of cybrids obtained from 'customized', patient-derived rho degree cells can have wide applications in the identification of respiratory chain defects originated by nuclear DNA-encoded mutations, and in the study of nuclear DNA-mitochondrial DNA interactions.
MINOR MESH HEADINGS: Cell-Line; Cytochrome-c-Oxidase-deficiency; DNA-; Electron-Transport-physiology; Fibroblasts-cytology; Fluorescent-Antibody-Technique; Hybrid-Cells; Leigh-Disease-enzymology; Oxidative-Phosphorylation; Transformation,-Genetic; Tumor-Cells,-Cultured
MAJOR MeSH HEADINGS: *Cell-Nucleus-genetics; *Cytochrome-c-Oxidase-genetics; *Leigh-Disease-genetics; *Mitochondria-genetics
NAME OF SUBSTANCE: Cytochrome-c-Oxidase; DNA
Record 30 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Inheritance and expression of mitochondrial DNA point mutations.
AUTHOR(S): Holme-E; Tulinius-MH; Larsson-NG; Oldfors-A
ADDRESS OF AUTHOR: Department of Clinical Chemistry, Gothenburg University, Sahlgren's Hospital, Sweden.
SOURCE (BIBLIOGRAPHIC CITATION): Biochim-Biophys-Acta. 1995 May 24; 1271(1): 249-52
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: An important feature of the mitochondrial genom is the occurrence of heteroplasmy and the possibility for transmission to the offspring of various proportions of wild-type and mutated mtDNA. We have investigated the proportion of the tRNALys A8344G mutation, the tRNALeu(UUR) A3243G mutation, and the ATPase 6 T8993G mutation in patients with MERRF, MELAS, and Leigh's syndrome and their maternal relatives. The level of mutated mtDNA in the offspring of carriers of the tRNALys mutation is correlated to the level in lymphocytes in the mother and seems to be transmitted by an essentially random mechanism where only a few mtDNA copies are founders of the mitochondrial genom in the offspring and the probability that the mutation is not transmitted to the offspring is high when the mothers carriers predominantly wild-type mtDNA. However, we found age-related differences in the distribution of mutated mtDNA in carriers of the tRNALys and tRNALeu mutations, which have to be considered before levels of mutated mtDNA are used for prediction of prognosis and transmission of a disorder.
MINOR MESH HEADINGS: Adolescence-; Adult-; Aged-; Aging-genetics; Aging-metabolism; Child-; Lymphocytes-metabolism; Middle-Age; Muscle,-Skeletal-growth-and-development; Muscle,-Skeletal-metabolism; Polymerase-Chain-Reaction; Probability-; RNA,-Transfer,-Leu-genetics
MAJOR MeSH HEADINGS: *DNA,-Mitochondrial-genetics; *H+-Transporting-ATP-Synthase-genetics; *Leigh-Disease-genetics; *MELAS-Syndrome-genetics; *MERRF-Syndrome-genetics; *Point-Mutation; *RNA,-Transfer,-Lys-genetics
NAME OF SUBSTANCE: H(+)-Transporting-ATP-Synthase; DNA,-Mitochondrial; RNA,-Transfer,-Leu; RNA,-Transfer,-Lys
Record 31 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Regulation of mitochondrial energy generation in health and disease.
AUTHOR(S): Kadenbach-B; Barth-J; Akgun-R; Freund-R; Linder-D; Possekel-S
ADDRESS OF AUTHOR: Fachbereich Chemie, Philipps-Universitat, Marburg, Germany.
SOURCE (BIBLIOGRAPHIC CITATION): Biochim-Biophys-Acta. 1995 May 24; 1271(1): 103-9
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: In mammalian cytochrome c oxidase (COX) three of the ten nuclear coded subunits (VIa, VIIa, VIII) occur in tissue-specific isoforms. The isoform distribution, however, varies in liver and heart of different species. Subunit VIII is different in liver and heart of bovine, dog, rat and chicken, but identical in human (liver-type) on one hand, and sheep, rabbit and rainbow trout (heart-type) on the other hand, as determined by N-terminal sequencing. Two moles of trinitrophenyl-ATP bind to monomeric COX from bovine heart and one to COX from bovine liver with dissociation equilibrium constant (Kd) values of about 3 microM. One binding site at the heart enzyme is blocked by a monoclonal antibody to subunit VIa-H. ATP (and/or ADP) interact with COX at two or three high-affinity binding sites, as shown by titration of the spectral changes of COX. Isolated COX from bovine heart was reconstituted with variable intraliposomal ATP/ADP ratios. By measuring the RCR (respiratory control ratio) and RCRVal (related to the valinomycin-respiration), which is a direct measure of the H+/e(-)-stoichiometry (Wilson and Prochaska, Arch. Biochem. Biophys. 282 (1990) 413-420), almost complete inhibition of the proton pump activity of COX by high intraliposomal ATP concentrations was found. The vectorial of protons for the formation of water, however, appears to be unaffected by nucleotides. This regulatory mechanism is assumed to have physiological significance for thermogenesis in muscle at rest. COX of fibroblasts from patients suffering from Leigh's syndrome, which is associated with a decreased COX activity, are suggested to have an incompletely assembled enzyme complex. This suggestion is further corroborated by the higher temperature-sensitivity of the enzyme when compared with COX from normal control fibroblasts. Defective regulation of COX via nuclear coded subunits is also proposed to cause mitochondrial diseases.
MINOR MESH HEADINGS: Amino-Acid-Sequence; Kinetics-; Mammals-; Mitochondria-ultrastructure; Mitochondria,-Heart-enzymology; Mitochondria,-Liver-enzymology; Models,-Biological; Molecular-Sequence-Data; Oxygen-Consumption; Protein-Structure,-Secondary; Reference-Values; Sequence-Homology,-Amino-Acid
MAJOR MeSH HEADINGS: *Cytochrome-c-Oxidase-chemistry; *Cytochrome-c-Oxidase-metabolism; *Disease-; *Energy-Metabolism; *Mitochondria-metabolism
NAME OF SUBSTANCE: Cytochrome-c-Oxidase
Record 32 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Neuronal degeneration in subacute necrotizing encephalomyelopathy (Leigh's disease). Case report.
AUTHOR(S): Lindboe-CF; Lie-AK; Aase-ST; Schjetne-OB; Haave-I
ADDRESS OF AUTHOR: Department of Pathology, Trondheim University Hospital, Norway.
SOURCE (BIBLIOGRAPHIC CITATION): APMIS. 1995 Jan; 103(1): 54-8
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: DENMARK
ABSTRACT: We report clinical, radiological and pathological findings in a 5-year-old girl who died of subacute necrotizing encephalomyelopathy (SNE) after 4 weeks of illness. Autopsy revealed endothelial swelling and vacuolar degeneration of the neuropil in the brain, brain stem and cerebellum. In addition, the affected areas showed degeneration of the neurons which was different from anoxic nerve cell damage both with regard to morphological picture and topographical distribution. This neuronal degeneration was probably due to the underlying metabolic defect in SNE per se and resembled in several aspects the nerve cell changes seen in the thalami and inferior olives in active Wernicke's encephalopathy. It is our opinion that more attention should be paid to the nerve cell degeneration in SNE rather than focusing on the relative preservation of these cells.
MINOR MESH HEADINGS: Autopsy-; Capillaries-pathology; Cerebellar-Cortex-pathology; Cerebellar-Nuclei-pathology; Cerebral-Cortex-blood-supply; Cerebral-Cortex-pathology; Child,-Preschool; Endothelium,-Vascular-pathology; Fatal-Outcome; Hemorrhage-pathology; Magnetic-Resonance-Imaging; Medulla-Oblongata-pathology; Mesencephalon-pathology
MAJOR MeSH HEADINGS: *Brain-pathology; *Leigh-Disease-pathology; *Nerve-Degeneration; *Neurons-pathology
Record 33 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy.
AUTHOR(S): De-Meirleir-L; Lissens-W; Benelli-C; Ponsot-G; Desguerre-I; Marsac-C; Rodriguez-D; Saudubray-JM; Poggi-F; Liebaers-I
ADDRESS OF AUTHOR: Department of Medical Genetics, Vrije Universiteit, Brussels, Belgium.
SOURCE (BIBLIOGRAPHIC CITATION): Pediatr-Res. 1994 Dec; 36(6): 707-12
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of "malaises." In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.
MINOR MESH HEADINGS: Base-Sequence; Infant-; Molecular-Sequence-Data; Mutation-; Pedigree-; Pyruvate-Dehydrogenase-Complex-Deficiency-Disease
MAJOR MeSH HEADINGS: *Central-Nervous-System-Diseases-genetics; *Exons-; *Leigh-Disease-genetics; *Pyruvate-Dehydrogenase-Complex-genetics; *RNA-Splicing
NAME OF SUBSTANCE: pyruvate-dehydrogenase-E1alpha-subunit; Pyruvate-Dehydrogenase-Complex
Record 34 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Proton spectroscopy in patients with Leigh's disease and mitochondrial enzyme deficiency [letter; comment]
COMMENTS: Comment on: Dev Med Child Neurol 1993 Sep;35(9):769-76
AUTHOR(S): Kruse-B; Hanefeld-F; Holzbach-U; Wilichowski-E; Christen-HJ; Merboldt-KD; Hanicke-W; Frahm-J
SOURCE (BIBLIOGRAPHIC CITATION): Dev-Med-Child-Neurol. 1994 Sep; 36(9): 839-43
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
MINOR MESH HEADINGS: Infant-; Leigh-Disease-enzymology; Mitochondria-enzymology; Nuclear-Magnetic-Resonance; Pyruvate-Dehydrogenase-Complex-Deficiency-Disease-diagnosis
MAJOR MeSH HEADINGS: *Brain-Chemistry; *Lactates-analysis; *Leigh-Disease-diagnosis
NAME OF SUBSTANCE: Lactates; Lactic-Acid
Record 35 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Isolated capillary proliferation in Leigh's syndrome.
AUTHOR(S): Matthews-PM; Nagy-Z; Brown-GK; Land-J; Squier-MV
ADDRESS OF AUTHOR: Department of Biochemistry, University of Oxford, England.
SOURCE (BIBLIOGRAPHIC CITATION): Clin-Neuropathol. 1994 May-Jun; 13(3): 139-41
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: GERMANY
ABSTRACT: An infant with hypotonia and recurrent apneic spells died with a diagnosis of pyruvate dehydrogenase deficiency and showed typical pathological changes of Leigh's syndrome at postmortem. Despite the prominence of symptoms suggesting dysfunction of brainstem respiratory centers during life, lesions were not found in the upper medulla. However, quantitative morphometric analysis demonstrated abnormal capillary hyperplasia in the region including and between the nucleus ambiguus and nucleus tractus solitarius. There was an average area of 8.0 +/- 2.5 x 10(6) mm2 occupied by capillaries per 0.75 mm2 field in the patient's brainstem, compared with 4.6 +/- 1.6 x 10(6) mm2 and 5.5 +/- 1.4 x 10(6) mm2 in two age-matched controls (p < 0.01). We speculate that capillary hyperplasia is a pathological marker of chronically impaired oxidative metabolism in the central nervous system in metabolic disease.
MINOR MESH HEADINGS: Brain-pathology; Capillaries-pathology; Infant-; Medulla-Oblongata-pathology; Pyruvate-Dehydrogenase-Complex-Deficiency-Disease-pathology; Respiratory-Center-pathology
MAJOR MeSH HEADINGS: *Leigh-Disease-pathology; *Medulla-Oblongata-blood-supply; *Neovascularization,-Pathologic-pathology; *Respiratory-Center-blood-supply
Record 36 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Mitochondrial DNA mutation underlying Leigh's syndrome: clinical, pathological, biochemical, and genetic studies of a patient presenting with progressive myoclonic epilepsy.
AUTHOR(S): Sweeney-MG; Hammans-SR; Duchen-LW; Cooper-JM; Schapira-AH; Kennedy-CR; Jacobs-JM; Youl-BD; Morgan-Hughes-JA; Harding-AE
ADDRESS OF AUTHOR: Department of Clinical Neurology, Institute of Neurology, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurol-Sci. 1994 Jan; 121(1): 57-65
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: An 18-year-old male patient presented with clinical and radiological evidence of Leigh's syndrome (LS), having developed progressive myoclonic epilepsy and ataxia 11 years previously. Muscle biopsy showed cytochrome oxidase deficiency but no ragged red fibres. Autopsy confirmed the diagnosis of LS; there was additional degenerative change in the cerebellum and dentate and olivary nuclei, and an axonal peripheral neuropathy. Biochemical studies showed reduced activity of complexes I and IV of the respiratory chain in mitochondria from heart, liver and kidney. The mutation of mitochondrial DNA (mtDNA) at position 8344, commonly associated with the syndrome of myoclonic epilepsy and ragged red fibres, was detected in the patient's blood and was present in muscle, brain, liver, heart, and kidney in uniformly high amounts. It is clear that LS is genetically heterogeneous and represents one of the most severe phenotypes of a number of different mtDNA defects.
MINOR MESH HEADINGS: Adolescence-; Base-Sequence; Brain-pathology; Leigh-Disease-physiopathology; Magnetic-Resonance-Imaging; Molecular-Sequence-Data
MAJOR MeSH HEADINGS: *DNA,-Mitochondrial-genetics; *Epilepsies,-Myoclonic-complications; *Leigh-Disease-genetics; *Leigh-Disease-pathology; *Mutation-
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 37 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Dystonia as the major manifestation of Leigh's syndrome.
AUTHOR(S): Lera-G; Bhatia-K; Marsden-CD
ADDRESS OF AUTHOR: University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, England, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Mov-Disord. 1994 Nov; 9(6): 642-9
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: We report eight patients who had a progressive illness dominated by generalised dystonia and who had clinical and imaging features suggestive of Leigh's syndrome (LS). Six of the eight cases were male. Early development was usually normal but three cases exhibited impaired mental and/or motor development, and three others had a history of an earlier unexplained encephalopathy or febrile illness. The onset of the dystonia occurred at a mean age of 3 years (range 2 months-7 years). All had abnormalities in the basal ganglia on brain imaging; symmetrical bilateral lucencies or calcification were seen in the basal ganglia on computed tomography scan in five cases, and high signal lesions were evident in these regions on T2-weighted magnetic resonance imaging sequences in seven cases. Other causes of such changes in the basal ganglia were excluded by appropriate investigations. Raised blood lactate levels were found in four of the eight patients. Muscle biopsies were done in seven patients but histology and histochemistry were normal. The common mitochondrial DNA mutations associated with LS in mitochondrial encephalopathies were not found in the six cases examined. LS presenting as a pure dystonic syndrome is uncommon, but should be considered in the differential diagnosis of symptomatic dystonia presenting in childhood.
MINOR MESH HEADINGS: Adolescence-; Adult-; Basal-Ganglia-pathology; Biopsy-; Child-; Diagnosis,-Differential; Dystonia-diagnosis; Dystonia-pathology; DNA-Mutational-Analysis; DNA,-Mitochondrial-genetics; Leigh-Disease-diagnosis; Leigh-Disease-pathology; Magnetic-Resonance-Imaging; Muscles-pathology; Neurologic-Examination
MAJOR MeSH HEADINGS: *Dystonia-etiology; *Leigh-Disease-complications
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 38 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Mitochondrial DNA 8993 (NARP) mutation presenting with a heterogeneous phenotype including 'cerebral palsy'.
AUTHOR(S): Fryer-A; Appleton-R; Sweeney-MG; Rosenbloom-L; Harding-AE
ADDRESS OF AUTHOR: Royal Liverpool Children's Hospital (Alder Hey), Department of Clinical Genetics.
SOURCE (BIBLIOGRAPHIC CITATION): Arch-Dis-Child. 1994 Nov; 71(5): 419-22
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: The mitochondrial DNA (mtDNA) mutation 8993 is an important cause of Leigh's encephalopathy. A family is reported where other affected members have presented with non-specific delayed development or cerebral palsy. The diagnosis should be considered not only in children with Leigh's encephalopathy, but also in those with mild neurological dysfunction (including cerebral palsy) if there is a pigmentary retinopathy or a family history of neurological or ophthalmological disease. There was some correlation in this family between the disease severity and the proportion of mutant mtDNA in the blood. This mutation appears to segregate to high levels of mutant mtDNA rapidly within pedigrees and the mother of a severely affected child has a high risk of having further children with a high proportion of mutant mtDNA and a severe phenotype.
MINOR MESH HEADINGS: Adolescence-; Adult-; Child-; Child,-Preschool; Infant-; Mental-Retardation-genetics; Pedigree-; Phenotype-; Retinitis-Pigmentosa-genetics
MAJOR MeSH HEADINGS: *Cerebral-Palsy-genetics; *Developmental-Disabilities-genetics; *DNA,-Mitochondrial-genetics; *Leigh-Disease-genetics; *Mutation-genetics
NAME OF SUBSTANCE: DNA,-Mitochondrial
Record 39 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Subacute necrotizing encephalopathy (Leigh's disease) in a child with particular reference to CT finding.
AUTHOR(S): Nitinavakarn-B; Shuangshoti-S
ADDRESS OF AUTHOR: Department of Radiology, Faculty of Medicine, Sri Nakarind Hospital, Khon Kaen University.
SOURCE (BIBLIOGRAPHIC CITATION): J-Med-Assoc-Thai. 1994 Dec; 77(12): 663-8
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: THAILAND
ABSTRACT: An example of subacute necrotizing encephalopathy, the fifth case in Thailand, was recorded. A 7-month-old boy presented clinically with vomiting, lethargy, respiratory difficulty, deteriorated consciousness, and hypotonia. The CT brain scan disclosed bilateral symmetrical radiolucencies in the basal ganglia, especially the lentiform nuclei, and thalami. Postmortem examination of these areas as well as the periaqueductal region revealed subacute necrotizing encephalopathy. It was characterized by necrosis, gliosis, and status spongiosus of the neuropil with relatively preserved neurons, and hyperplasia of small blood vessels as well as endothelium. As far as we are aware, the vast majority of abnormalities in the basal ganglia visualized by CT brain imaging often show calcific foci or high attenuation with asymmetrical distribution. Bilateral symmetrical lesions of low density are rare. We reported such an abnormality in a postmortem proven case of Leigh's disease. To recognize this finding should lead to correct antemortem diagnosis of the latter.
MINOR MESH HEADINGS: Basal-Ganglia-pathology; Fatal-Outcome; Infant-; Leigh-Disease-pathology
MAJOR MeSH HEADINGS: *Basal-Ganglia-ultrasonography; *Leigh-Disease-ultrasonography
Record 40 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Is Purkinje cell loss in Leigh's disease an excitotoxic event secondary to damage to inferior olivary nuclei?
AUTHOR(S): Cavanagh-JB
ADDRESS OF AUTHOR: Department of Neurology, Institute of Psychiatry, Kings College Hospital Medical School, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Neuropathol-Appl-Neurobiol. 1994 Dec; 20(6): 599-603
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: In a series of 17 cases of Leigh's disease it has been observed that there is a close correlation between damage to the inferior olivary nuclei by vasculo-necrotic change and loss of Purkinje cells in the cerebellar cortex. It is suggested that this association may be explained on the basis of the selective loss of climbing fibres causing increased firing activity of Purkinje cells with consequent excessive entry of calcium ions. In these circumstances control of calcium ion regulation in the presence of reduced energy production, which is the basis of this metabolic disease, would be expected to put these cells' survival seriously at risk.
MINOR MESH HEADINGS: Age-Factors; Cell-Count; Child-; Child,-Preschool; Infant-; Infant,-Newborn; Substantia-Nigra-pathology
MAJOR MeSH HEADINGS: *Cerebellum-pathology; *Leigh-Disease-pathology; *Olivary-Nucleus-pathology; *Purkinje-Cells-pathology
Record 41 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Pathogenic factors underlying the lesions in Leigh's disease. Tissue responses to cellular energy deprivation and their clinico-pathological consequences.
AUTHOR(S): Cavanagh-JB; Harding-BN
ADDRESS OF AUTHOR: Department of Neurology, King's College Hospital Medical School, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Brain. 1994 Dec; 117 ( Pt 6): 1357-76
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: In a search for pathogenic factors that might play roles in the selective vulnerability of brain regions to the lesions of Leigh's disease, archival material from 20 cases of this condition, dying between 1975 and 1992 and aged from 4 days to 11.75 years at death, have been examined. Attention was paid to the topography of the lesions, their nature and timing in the evolution of the disease, the clinico-pathological correlations and the ages of the subjects at onset and at death. The following observations would appear to be explicable in terms of the present understanding that impairment of cellular energy generation is known to be defective in some, and probably all, cases. (i) The characteristic lesion of this disease is symmetrical vasculonecrotic damage affecting several brainstem centres, the topography of which is variable and may partly depend upon the age of the individual. (ii) Early features of this lesion are indistinguishable from a small partial infarction and progress similarly. The size of the damaged area is generally related to the size of the region affected. There is no haemorrhagic component and haemosiderin is not at any time found, unlike the lesions of Wernicke's disease. (iii) The process is episodic and total tissue damage is thus cumulative. More than one episode of damage may be seen in a region, changes of clearly different ages being often present together. (iv) In some regions the lesions appear to be age dependent, e.g. inferior olivary nuclei, and may be related to behavioral development and neuronal activity. Other regions show damage at any age, e.g. substantia nigra. (v) Myelin and sometimes axon loss in optic pathways is usually central, the periphery being spared. This occurred in more than half the cases and may represent a partial infarct-like change. (vi) The characteristic dorsal spinal column degeneration is always associated with focal necrosis of central grey and white matter; this also resembles a partial infarction with secondary ascending degeneration. (vii) Massive myelin loss in the centra semiovalia occurred in one-third of the cases, with or without cavitation, often in association with spongy myelin changes elsewhere. A mild general spongy change in myelin alone occurred in two cases. The massive lesions are focal, infarct-like and analogous to Binswanger's disease. (viii) Selective neuronal loss, common in some mitochondrial disorders, is not a major feature of Leigh's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
MINOR MESH HEADINGS: Brain-blood-supply; Brain-metabolism; Cerebral-Cortex-pathology; Energy-Metabolism; Infant-; Infant,-Newborn; Leigh-Disease-metabolism; Myelin-Sheath-pathology; Neurons-pathology; Spinal-Cord-pathology
MAJOR MeSH HEADINGS: *Brain-pathology; *Leigh-Disease-pathology
Record 42 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Mitochondrial DNA alterations and genetic diseases: a review.
AUTHOR(S): Lestienne-P; Bataille-N
ADDRESS OF AUTHOR: U 298 INSERM, CHRU Angers, France.
SOURCE (BIBLIOGRAPHIC CITATION): Biomed-Pharmacother. 1994; 48(5-6): 199-214
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: FRANCE
ABSTRACT: We review the main features of human mitochondrial function and structure, and in particular mitochondrial transcription, translation, and replication cycles. Furthermore, some pecularities such as mitochondria's high polymorphism, the existence of mitochondrial pseudogenes, and the various considerations to take into account when studying mitochondrial diseases will also be mentioned. Mitochondrial syndromes mostly affecting the nervous system have, during the past few years, been associated with mitochondrial DNA (mt DNA) alterations such as deletions, duplications, mutations and depletions. We suggest a possible classification of mitochondrial diseases according to the kind of mt DNA mutations: structural mitochondrial gene mutation as in LHON (Leber's Hereditary Optic Neuropathy) and NARP (Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa) as well as some cases of Leigh's syndrome; transfer RNA and ribosomal RNA mitochondrial gene mutation as in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike Episodes) or MERRF (Myoclonic Epilepsy with Ragged Red Fibers) or deafness with aminoglycoside; structural with transfer RNA mitochondrial gene mutations as observed in large-scale deletions or duplications in Kearns-Sayre syndrome, Pearson's syndrome, diabetes mellitus with deafness, and CPEO (Chronic Progressive External Ophtalmoplegia). Depletions of the mt DNA may also be classified in this category. Even though mutations are generally maternally inherited, most of the deletions are sporadic. However, multiple deletions or depletions may be transmitted in a mendelan trait which suggests that nuclear gene products play a primary role in these processes. The relationship between a mutation and a particular phenotype is far from being fully understood. Gene dosage and energic threshold, which are tissue-specific, appear to be the best indicators. However, the recessive or dominant behavior of both the wild type or the mutated genome appears to play a significant role, which can be verified with in vitro studies.
MINOR MESH HEADINGS: Genes,-Structural; Mutation-; RNA,-Ribosomal-genetics; RNA,-Transfer-genetics
MAJOR MeSH HEADINGS: *DNA,-Mitochondrial-genetics; *Genetics,-Medical-classification
NAME OF SUBSTANCE: DNA,-Mitochondrial; RNA,-Ribosomal; RNA,-Transfer
Record 43 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: MtDNA and nuclear mutations affecting oxidative phosphorylation: correlating severity of clinical defect with extent of bioenergetic compromise.
AUTHOR(S): Robinson-BH
ADDRESS OF AUTHOR: Department of Biochemistry, University of Toronto, Ontario, Canada.
SOURCE (BIBLIOGRAPHIC CITATION): J-Bioenerg-Biomembr. 1994 Jun; 26(3): 311-6
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Rates of ATP synthesis were studied in cultured skin fibroblasts treated with digitonin. In fibroblasts from patients with complex I deficiency, complex IV and complex V deficiency rates of ATP synthesis were decreased below the levels found in controls. In mitochondria isolated from cultured lymphoblasts, ATP synthesis was also decreased by 35-50% in cases of Leigh's disease due to complex I, complex IV, or complex V deficiency. Calculating the effect of the mutations in the various complexes on the overall efficiency of oxidative phosphorylation, we show that the mtDNA 8993 mutation which affects the activity of the F1F0 ATPase (complex V) has the strongest effect.
MINOR MESH HEADINGS: Adenosine-Triphosphate-biosynthesis; Adenosinetriphosphatase-antagonists-and-inhibitors; DNA,-Mitochondrial-analysis; Leigh-Disease-genetics; Mitochondria-ultrastructure; Mitochondrial-Myopathies-genetics; Oxidative-Phosphorylation; Phenotype-
MAJOR MeSH HEADINGS: *DNA,-Mitochondrial-genetics; *Energy-Metabolism-genetics; *Leigh-Disease-metabolism; *Mitochondria-metabolism; *Mitochondrial-Myopathies-metabolism; *Point-Mutation
NAME OF SUBSTANCE: Adenosinetriphosphatase; DNA,-Mitochondrial; Adenosine-Triphosphate
Record 44 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Mitochondrial DNA mutations in diseases of energy metabolism.
AUTHOR(S): Wallace-DC
ADDRESS OF AUTHOR: Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322.
SOURCE (BIBLIOGRAPHIC CITATION): J-Bioenerg-Biomembr. 1994 Jun; 26(3): 241-50
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: A variety of degenerative diseases involving deficiencies in mitochondrial bioenergetics have been associated with mitochondrial DNA (mtDNA) mutations. Maternally inherited mtDNA nucleotide substitutions range from neutral polymorphisms to lethal mutations. Neutral polymorphisms are ancient, having accumulated along mtDNA lineages, and thus correlate with ethnic and geographic origin. Mildly deleterious base substitutions have also occurred along mtDNA lineages and have been associated with familial deafness and some cases of Alzheimer's Disease and Parkinson's Disease. Moderately deleterious nucleotide substitutions are more recent and cause maternally-inherited diseases such as Leber's Hereditary Optic Neuropathy (LHON) and Myoclonic Epilepsy and Ragged-Red Fiber Disease (MERRF). Severe nucleotide substitutions are generally new mutations that cause pediatric diseases such as Leigh's Syndrome and dystonia. MtDNA rearrangements also cause a variety of phenotypes. The milder rearrangements generally involve duplications and can cause maternally-inherited adult-onset diabetes and deafness. More severe rearrangements frequently involving detections have been associated with adult-onset Chronic Progressive External Ophthalmoplegia (CPEO) and Kearns-Sayre Syndrome (KSS) or the lethal childhood disorder, Pearson's Marrow/Pancreas Syndrome. Defects in nuclear-cytoplasmic interaction have also been observed, and include an autosomal dominant mutation causing multiple muscle mtDNA deletions and a genetically complex disease resulting in the tissue depletion of mtDNAs. MtDNA nucleotide substitution and rearrangement mutations also accumulate with age in quiescent tissues. These somatic mutations appear to degrade cellular bioenergetic capacity, exacerbate inherited mitochondrial defects and contribute to tissue senescence. Thus, bioenergetic defects resulting from mtDNA mutations may be a common cause of human degenerative disease.
MINOR MESH HEADINGS Aging-; Chromosome-Aberrations; DNA,-Mitochondrial-analysis
MAJOR MeSH HEADINGS *DNA,-Mitochondrial-genetics; *Energy-Metabolism; *Metabolic-Diseases-genetics; *Mitochondrial- Myopathies- genetics; *Mutation-
NAME OF SUBSTANCE DNA,-Mitochondrial.
Record 45 of 45 in MEDLINE EXPRESS (R) 1994-1996
TITLE: Subacute necrotizing encephalomyelopathy (Leigh's disease) [letter; comment]
COMMENTS: Comment on: J Paediatr Child Health 1993 Oct;29(5):363-7
AUTHOR(S): Bourne-AJ
SOURCE (BIBLIOGRAPHIC CITATION): J-Paediatr-Child-Health. 1994 Jun; 30(3): 283-5
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: AUSTRALIA
MINOR MESH HEADINGS: Biopsy-; Diagnosis,-Differential; Infant-; Leigh-Disease-blood; Muscles-pathology; Reproducibility-of-Results
MAJOR MeSH HEADINGS: *Canavan-Disease-pathology; *Leigh-Disease-pathology
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